1 - SYSTEMIC RETINOIDS Flashcards
Tretinoin (Retrieve cream) is all-trans-retinoic acid
True
Isotretinoin is 13-cis retinoic acid
True
Isotretinoin (13-cis retinoic acid) and tretinoin (all-trans-retinoic acid) are first generation retinoids (non-aromatic retinoids)
True
Acitretin is a second generation retinoid (monoaromatic retinoids)
True
Acitretin is an acid metabolite of another second generation retinoid etretinate (phased out due to prolonged presence in subcutaneous fat)
True
Topical Tazarotene, topical Adapalene, Bexarotene are third generation retinoids (polyaromatic retinoids)
True
Tretinoin, Isotretinoin (both first generation retinoids), Acitretin (second generation retinoid) and bexarotene (third generation retinoid) are bound to plasma proteins with the former 3 bound specifically to albumin
True
All retinoids are metabolised in the liver by CYP3A4
True
Acitretin has a higher bioavailability than Isotretinoin
True (60% vs 25%)
Tretinoin, Isotretinoin and Acitretin are excreted in the bile (faeces) and urine
True
Bexarotene is excreted in the bile and urine
False (only hepatobiliary)
Retinoids are vitamin A derivatives
True
Vitamin A can be synthesised in vivo
False (must be acquired through the diet)
Beta-carotene (a carotenoid) is a precursor of vitamin A and is converted to retinal (vitamin A aldehyde)
True
Retinal (vitamin A aldehyde) the 11-cis isomer and 11-trans isomer is important in the biochemical reaction of visual function
True
Retinol (vitamin A alcohol) is essential to reproduction
True
Retinol (vitamin A alcohol) and retinal (vitamin A aldehyde) can be converted interchangeably
True
Retinol (vitamin A alcohol) is irreversibly metabolised to retinoic acid
True
Retinal (vitamin A aldehyde) and retinoic acid play an essential role in epithelial differentiation and normal growth
True
Third generation retinoids are more potent than earlier generation retinoids and their therapeutic index (efficacy:toxicity ratio) shows no signs of improvement due to increased toxicity
True
The oral bioavailability of retinoids is reduced with food intake
False (enhanced with food intake especially fatty food)
Isotretinoin, Acitretin and Bexarotene are relatively water soluble
True (Isotretinoin and Acitretin undetectable in serum within 1 month after stopping therapy)
The hepatic metabolism of retinoids is induced mainly by retinoids themselves but also by other agents known to induce hepatic CYP3A4
True
Tretinoin has the shortest half life
True (tretinoin - bexarotene - Isotretinoin - Acitretin)
Acitretin has the longest half life
True (tretinoin - bexarotene - Isotretinoin - Acitretin)
Acitretin (50 hours) has a longer half life than Isotretinoin (10-20 hours)
True (tretinoin - bexarotene - Isotretinoin - Acitretin)
Isotretinoin (10-20 hours) has a longer half life than bexarotene (7-9 hours)
True (tretinoin - bexarotene - Isotretinoin - Acitretin)
Alcohol indirectly enhances the re-esterification of Acitretin to Etretinate (lipophilic second generation retinoid that preceded its acid metabolite Acitretin which is stored and slowly released from adipose tissue resulting in a prolonged half life of 2.9 years)
True (this re-esterification is the reason why contraception for 3 years after cessation of Acitretin is recommended in women of child bearing age)
Retinoids are small molecule hormones that elicit their biological effects by activating nuclear receptors and regulating gene transcription
True
Retinoids exert their physiologic effects by binding to receptors present in the nucleus
True
There are 2 families of retinoid receptors - retinoic acid receptor (RAR) family and retinoid X receptor (RXR) family
True
The retinoic acid receptor (RAR) family has 3 Isoforms - alpha, beta and gamma
True (same as RXR)
The retinoid X receptor (RXR) family has 3 Isoforms - alpha, beta and gamma
True (same as RAR)
Retinoic acid receptors (RAR) are always and exclusively paired with Retinoid X receptors (RXR)
True
Retinoid X receptor (RXR) can exist as a homodimer with another retinoid X receptor (RXR)
True (whereas RAR needs to be paired with an RXR)
Retinoid X receptor (RXR) may be paired with another RXR, a Retinoic acid receptor (RAR), vitamin-D3 receptor, thyroid hormone receptor, and peroxisome proliferator-activated receptor
True
There are a total of 6 Isoforms of retinoid receptors - RAR alpha, beta, gamma and RXR alpha, beta, gamma receptors
True
Retinoid receptors are part of a large superfamily of receptors consisting also of glucocorticosteroid, thyroid hormone and vitamin-D3 receptors
True
Acitretin (second generation retinoid) has a weak interaction with multiple Retinoid Acid Receptors (RAR) by activating these receptors but not binding to them
True
Alitretinoin (third generation retinoid) is a pan-retinoid receptor and binds to all 6 known retinoid receptors (RAR alpha, beta, gamma and RXR alpha, beta, gamma)
True
Tretinoin (First generation retinoid) binds to RAR
True
Isotretinoin (First generation retinoid) has no clearly identified affinity for any retinoid receptor (RAR or RXR)
True
There is a higher affinity for RXR than RAR with the higher generation retinoids
True (third generation Retinoids Alitretinoin and Bexarotene have a higher affinity for RXR)
Topical retinoids Adapalene and Tazarotene (third generation retinoids) binds to RAR beta and gamma Isoforms
True (in contrast to the other systemic and topical third generation retinoid Bexarotene which has an affinity for RXR instead of RAR)
Systemic retinoids affect the pathways involved in inflammation
True
Systemic retinoids affect the pathways involved in cellular differentiation
True